Neuropathological examination of the brains from patients with Alzheimer's disease (AD) have revealed deposits of two types of abnormal fibers. These are the paired helical filaments making the neurofibrillary tangles and amyloid fibers in plaques and vessels. Several laboratories have provided evidence that the main protein component of both cerebrovascular and plaque amyloid is AD is beta-protein. Recently the molecular cloning and characterization of cDNAs encoding the beta-protein precursor have been reported. Structural studies of the protein indicates that the amyloid precursor protein is a cell surface protein. We have selected amino acid segments from regions of the protein that are thought to lie (a) outside the cell, (b) in the cell membrane and (c) in the cytoplasm. Three different peptides, each 19-24 amino acids in length, that correspond to these protein segments were synthesized by using an automated peptide synthesizer. Rabbit antisera are being produced against these carrier-linked synthetic peptides. Because amyloid proteins are degraded in the brains of AD patients, fragments may be found in CSF. Thus we propose to quantitate the level of synthetic peptides in CSF from patients with AD, using specific antisera to the peptides and a sensitive enzyme linked immunosorbent assay. Since there is no specific laboratory test for the diagnosis of AD, detection of higher levels of amyloidogenic peptides in CSF may be a useful marker in the diagnosis of the disease.